TiO2 Nanosheets with the Au Nanocrystal-Decorated Edge for Mitochondria-Targeting Enhanced Sonodynamic Therapy

Sonodynamic therapy (SDT) has attracted much attention since it can break the depth-penetration barrier of phototriggered therapeutic strategies. However, developing sonosensitizers with a high reactive oxygen species (ROS) quantum yield for precision and enhanced SDT remains a major challenge. In this study, Au nanocrystals were selectively grew on the edge of the TiO2 nanosheets (NSs) with highly exposed (001) facets to fabricate Au-TiO2 NSs as sonosensitizers for enhanced SDT. The high sonosensitization efficiency was closely linked to the effective prevention of the fast recombination of excited electrons and holes. Under ultrasound (US) irradiation, the ROS generation efficiency of the resulting Au-TiO2 NSs was higher compared to pure TiO2 NSs and superior to previous TiO2 nanocomposite. The Au-TiO2 was further modified with mitochondria-targeted triphenylphosphine (TPP) and AS1411 aptamer (Au-TiO2-A-TPP) to realize organelle-targeted enhanced SDT and CT (computed tomography) imaging. The tumor growth inhibition was completely realized via Au-TiO2-A-TPP-mediated SDT both in vitro and in vivo due to the adequate ROS generation in the mitochondria organelle. This knowledge is vital to design an inorganic sonosensitizer with structure-dependent and mitochondria-target related SDT enhancement.